This year the NHLBI CPS team has been heavily invested in research related to SHARe (SNP Health Association Resource), and in planning for the SABRe CVD Initiative (Systems Approach to Biomarker Research in Cardiovascular Disease). [unreadable] [unreadable] I. Dr. Levy[unreadable] Much of Dr. Levy'd personal scientific effort in 2008 has been devoted to two efforts: a) hypertension genetics and b) biomarker research. [unreadable] A) Dr. Levy is leading Framingham efforts in the area of hypertension genetics. This effort comprises 3 elements: i) Leader of the SHARe Blood Pressure Working Group, ii) Leader of the CARe Blood Pressure Working Group, and iii) Resequencing projects directed at hypertension candidate genes. In conjunction with SHARe, Dr. Levy hasestablished a consortium with investigators from Framingham, ARIC, Rotterdam, CHS, and AGES. Preliminary blood pressure GWAS results are available from 3 of those studies and we are in the process of completing a meta-analysis of results across all 5 participating observational studies. We successfully identified genomewide significant associations with hypertension, our primary publication was submitted to Nature Genetics and it sheds light on the genetic underpinnings of hypertension. Similarly, as leader of the CARe Blood Pressure Working Group, we will be analyzing 2500 cardiovascular candidate genes in relation to blood pressure. Third, Dr. Levy is co-PI (with Chris Newton-Cheh) of a resequencing study that will characterize rare variants in 23 BP candidate genes. We are in the process of genotyping about 250 variants (mostly missense) in these genes that are differentially present at the low or high extremes of blood pressure. We expect to complete this genotyping in 7000 Framingham participants in late 2008 and should have results in hand in early 2009.[unreadable] [unreadable] B) Much of Dr. Levy's effort in 2008 has been devoted to planning for the SABRe CVD Initiative. We are nearing finalization of a CRADA to conduct state-of-the-art discovery metabolomics and proteomics of atherosclerosis and of metabolic syndrome. We also are nearing the start of a feasibility study of gene expression profiling in 3 sources of WBC-derived RNA from Framingham participants that will be conducted in collaboration with the NHLBI Core Microarray Lab. If technical feasibility can be demonstrated for one or more RNA sources, we plan to move forward with a large-scale study of gene expression in 7000 Framingham individuals. When this resource is combined with the SHARe database, we will be able to catalog genetic contributions to gene expression and the relations of common genetic variation and gene expression to disease phenotypes. I have met with David Lipman and Jim Ostell to plan for NCBI to create a resource of gene expression data and to make this accessible to the outside scientific community in a manner similar to the SHARe resource.[unreadable] [unreadable] II. Dr. Fox[unreadable] Dr. Fox's scientific focus has been on research in the areas of metabolic disorders (obesity and diabetes) and kidney disease.[unreadable] A) In the area of obesity, Dr. Fox successfully mentored several post-doctoral fellows to create several CT fat datasets related to pericardial fat, fatty liver, and peri-aortic fat. These have resulted in several manuscripts that are currently being revised. Dr. Fox led the CHARGe obesity working group, which is an international consortium. They are putting our first paper together now.[unreadable] B) In the area of diabetes, Dr. Fox mentored Sarah Rosner (IRTA fellow) in a study of temporal trends in diabetes-related mortality, which resulted in a travel award at CVD Epidemiology meeting. Sarah also is submitted 2 CVD epi abstracts for 2009. Dr. Fox also participated in several glycemic traits related projects in terms of candidate gene studies and genome-wide association.[unreadable] 3) Kidney disease research efforts included mentoring of Meredith Foster (post-bac fellow) through several obesity and CKD papers, and the collection of a fatty kidney dataset for her doctoral dissertation at the Harvard School of Public Health. Dr. Fox also successfully collaborated with the ARIC study for 1.5 years for CKD genetics, which has resulted in 2 collaborative publications. In the CHARGe kidney disease working group, Dr. fox led an international consortium to study the genetics of renal disease and related traits. This has resulted in one paper in press at the Lancet exploring the genetics of uric acid and gout.